Evaluation of atomoxetine for first-line treatment of newly diagnosed, treatment-naïve children and adolescents with attention deficit/hyperactivity disorder

Abstract

Objective:

To test the hypothesis that first-line treatment with atomoxetine provides superior efficacy than placebo for up to 12 weeks in improving the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD).

Research design and methods:

This double-blind, randomized, placebo-controlled, parallel clinical trial included 151 treatment-naïve children (n = 113) and adolescents (n = 38) with newly diagnosed (≤3 months) ADHD. Atomoxetine dose was uptitrated from 0.5 to 1.2 mg/kg/day after two weeks. Outcome assessments included the ADHD Rating Scale-IV-Parent-reported Investigator-rated (ADHDRS-IV-Parent:Inv), the Clinical Global Impression of Severity of ADHD (CGI-ADHD-S), and the incidence of adverse events. Mixed-model repeated measures analysis was used to compare scale score changes between groups.

Clinical trial registration:

Trial registered at www.clinicaltrials.gov (study internal code: B4Z-XM-LYDM, identifier: NCT00191945).

Results:

Most patients were male (79.2%), of caucasian origin (96.0%) and severely ill (72.5%). Their mean age was 10.3 years. Atomoxetine-treated patients showed greater reductions from baseline to week 12 of total ADHDRS-IV-Parent:Inv score than placebo-treated patients (least square mean difference: −7.9 [95% CI: −11.0 to −4.8], corresponding to a large effect size of 0.8). Between-group mean differences increased progressively with treatment exposure from week 6 to 12 (−2.7 [−4.9 to −0.6] for total and −1.6 [−2.9 to −0.3] for inattention scores). At the end of the study, 50% of atomoxetine-treated patients (14% with placebo) showed a reduction ≥40% in total ADHDRS-IV-Parent:Inv score, and only 29% (46% with placebo) were severely ill (by CGI-ADHD-S). Treatment-related adverse events were significantly more frequent with atomoxetine (65.0%) than with placebo (37.3%), the most frequent being decreased appetite and somnolence. Only one case of decreased appetite was rated as severe. No patient discontinued treatment because of adverse events.

Conclusions:

A continued improvement of symptoms is expectable until 12 weeks in treatment-naïve ADHD patients treated with atomoxetine as first-line medication. Chief limitations are the small, national sample size and the absence of data beyond the 12-week time-point.

Key words::

• Attention Deficit Disorder with Hyperactivity
• Atomoxetine
• Randomized controlled trial
• Psychometrics

Transparency

Declaration of funding

This clinical trial has been funded by Lilly Research Laboratories, Alcobendas, Spain.

Declaration of financial/other relationships

A.M., M.J.G.-P., I.G., and R.E. are full-time employees of Eli Lilly and Company or its affiliates. A.H. has received fees from Eli Lilly, Shire and Janssen–Cilag as consultant and from Eli Lilly and Janssen–Cilag as lecturer. J.A. has received fees from Eli Lilly and Janssen–Cilag as coordinator of courses on conduct and learning disorders and from Eli Lilly as clinical investigator. E.C., J.A.A., and X.G. have received fees from Eli Lilly as clinical investigators. M.J.M. has received fees from Eli Lilly as lecturer and as clinical investigator.

Acknowledgments

The authors wish to thank the following atomoxetine LYDM investigators for their participation in this study: Joaquín Fuentes, Marta García, Óscar Herreros, María-Jesús Mardomingo, José-Ramón Gutiérrez, Fernando Mulas, José-Angel Alda, Tomás Cantó, Lidia Riera, Montserrat Jimenez, Encarna Calderon, Silvia Delgado, Katy Garcia, Eugenia Rigau, Rosa Calvo, Petra Sánchez, Elena Parra, Amalia Espinosa, Aída Pérez, Irma Isasa, Belén García, Rubén Gandía, Silvia Pérez, Coloma Palmer, María-José Costa, Milagros Fuentes.

The results of this study were previously presented in the 13th International Congress of the European Society for Child and Adolescent Psychiatry (ESCAP), Florence, 25–29 August 2007.

The authors also wish to thank Medicxact that acted as an external Medical Writing services provider and, in particular, Jesús Villoria, who drafted the manuscript, and provided technical and editorial assistance. M.J.G.P. acted as statistical expert for this study.